The focus on living longer and reducing aging has been with us humans since the day we started walking the earth. Vitamins, elixirs, charms and all manner of strange practices have claimed to slow or reverse the aging process and prevent age-related diseases.
But so far, most of them are worthless, sorry to say. Outside of diet and exercise, most anti-aging miracles don’t stand up to scientific scrutiny. (There is even some debate about the merits of diet and exercise — a discussion for another day.)
NAD+: A Fountain of Youth?
Recently, NAD+ (nicotinamide adenine dinucleotide) precursors have gotten a lot of attention for their possible effects of slowing down the aging process. Fair warning, we are going to get into some nerdy science here. Read on if you are up for it. If you want a Cliffs Notes version, the conclusions are at the end.
NAD alternates between two forms: NAD+ (oxidized form) and NADH (reduced form). NAD+ is a co-factor for many enzymes in the body. NAD+ is a coenzyme found in all living cells, facilitating oxidation and reducing reactions (loss or gain of electrons) in the body. NAD+ is required for the fundamental biological processes that make life possible, and levels decline as we age.
Scientists have known about NAD+ since it was first discovered in 1906. Since then, our understanding of its importance has continued to evolve. NAD+ precursors played a role in mitigating pellagra — a fatal disease that plagued the American south in the 1900s.
NAD+ levels decrease with age and with the onset of some diseases. This decrease in NAD+ levels leads to a decrease in sirtuin activity. (Sirtuins are a family of proteins that play a role in aging by regulating cellular health.) In addition, studies in yeast roundworms and fruit flies suggest that increased levels of NAD+ and increased activity of the sirtuin enzyme are associated with an increased lifespan.
Sirtuins: A Key to Longevity
Why should these studies have relevance to us humans? It turns out the sirtuin enzymes are found across species all the way up to humans.
The commonality of enzyme pathways across species generally indicates that it’s of great importance to the cells in which the enzyme is found. In addition, enzymes, in general, will have similar functions across species. So increased longevity in these other species could be relevant to us humans.
What is the direct evidence for a beneficial effect of NAD+ precursors on longevity in humans? The short answer is — there isn’t any.
There is a very good reason for that. Studies on human longevity are long, expensive, and fraught with scientific uncertainty. We humans, relative to most other creatures, live a long time. Studies in humans would require decades of data collection. Humans also introduce a number of experimental factors that cannot be controlled.
Humans chosen or volunteering for any study would be genetically diverse. In addition, the population of humans in the study would have been exposed to different environmental factors (food, stress, toxins, etc.) prior to the study and during the study, which could skew the findings.
Studying Diseases That Affect Longevity
Because longevity studies in humans are so difficult and costly, they are unlikely to be undertaken by anyone. However, diseases associated with some of the major causes of human mortality can be studied. For example, heart disease is the most common cause of death in the US today.
The four horsemen of this personal apocalypse are increased blood pressure, decreased insulin sensitivity (a pre-diabetic state), hyperlipidemia (increased cholesterol and triglycerides in the blood) and obesity. So rather than looking at longevity directly, looking at the effects of NAD+ precursors on these factors is more straightforward.
NAD+ precursor supplementation in animals has been shown to decrease weight gain, increase insulin sensitivity, and increase glucose tolerance. Precursor supplementation has also been shown to improve cardiac function in mice. NAD+ precursor supplementation may also have positive effects on liver and neuronal function.
There is enough evidence from these animal studies to warrant investigation of NAD+ precursors in humans. Recent clinical studies have shown that oral administration of NAD+ precursors increased the levels of NAD+ in the blood. This indicates that the precursors can be effectively absorbed from the gastrointestinal tract and into tissues to be converted into NAD+.
It Couldn’t Hurt
NAD+ precursor administration in these studies had no serious side effects. A recent clinical study showed that NR supplementation produced a decreased blood pressure in healthy adults.
Bottom line? Substantial animal data exists that suggests NAD+ precursor supplements have beneficial effects on the body as we age. Clinical studies show that taking oral NAD+ precursor supplements does raise NAD+ levels, and a preliminary study suggests it may have cardiovascular benefits. And taking them has no negative side effects.
Taken together, it’s encouraging, but still not conclusive. Further investigation is clearly warranted. If you are over 50, and you want to hedge your bets and don’t mind spending the money ($40-$60 per month) there is no negative effect to taking NAD+ precursors.
Do we take them? Yes. Do we feel better? Hard to tell. Will we live longer? Maybe.
Imai, S and Guarente, L. (2016) It Takes Two to Tango: NAD+ and Sirtuins in Aging/Longevity Control. NPJ Aging Mech Dis 2: 16017. Doi: 10.1038/npjamd.2016.17.
Fletcher, RS and Lavery, GG (2018) The Emergence of the Nicotinamide Riboside Kinases in the Regulation of NAD+ Metabolism. J Mol Endocrinol 61: R107-R121. doi: 10.1530/JME-18-0085.
Johnson, S and Imai, S. (2018) NAD + Biosynthesis, Aging, and Disease. F1000Res. 1:132. doi: 10.12688/f1000research.12120.1
Kane, AE, and Sinclair, DA. (2018) Sirtuins and NAD+ in the Development and Treatment of Metabolic and Cardiovascular Disease. Circ Res 123: 868-885. doi: 10.1161/CIRCRESAHA.118.312498.
Braidy, N et al., (2019) Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes. Antioxid Redox Signal. 30: 251–294. (Published online 30Nov2018).
Brenner, Charles. Personal communication via email. Nov-Dec 2018. (Charles Brenner, Ph.D. is the Roy J. Carver Chair of Biochemistry and Professor of Internal Medicine and Founding Co-Director of the University of Iowa Obesity Research and Education Initiative at the Carver College of Medicine at the University of Iowa. Dr. Brenner is also the Chief Scientific Advisor to ChromaDex, the company that produces Niagen® and TruNiagen®.)
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